2018 年第 8 期 第 13 卷

迷走神经对血管紧张素Ⅱ介导的小鼠高血压心脏纤维化进程的抑制作用研究

Vagus nerve inhibits angiotensin Ⅱ-mediated cardiac fibrosis in hypertensive mice

作者：李玉琳李国旗张聪聪杜杰

英文作者：

单位：100029首都医科大学附属北京安贞医院北京市心肺血管疾病研究所心血管生物研究室

英文单位：

关键词：迷走神经;高血压;心脏纤维化;CD+45白细胞浸润

英文关键词：

• 摘要：

• 【摘要】目的    观察迷走神经对血管紧张素Ⅱ（AngⅡ）介导的小鼠高血压心脏纤维化进程的抑制作用。方法    选择雄性12周龄C57BL/6J小鼠36只，按照随机数字表法分为4组：假手术+0.9%氯化钠溶液灌注组（A组）、左侧迷走神经切除+0.9%氯化钠溶液灌注组（B组）、假手术+AngⅡ灌注组（C组）、左侧迷走神经切除+AngⅡ灌注组（D组）。采用Masson法观察4组小鼠心脏间质中胶原的沉积，采用苏木精-伊红和麦胚凝集素染色法检测心肌细胞肥厚面积，采用实时荧光定量聚合酶链反应法检测心脏组织中肿瘤坏死因子α、白细胞介素1β、白细胞介素6的表达。结果    与A组和B组比较，C组和D组术后1~7 d收缩压均显著升高（均P＜0.05）。D组小鼠心脏纤维化面积大于C组［（6.40±0.53）%比（4.30±0.25）%］，小鼠心脏组织α-平滑肌肌动蛋白mRNA、转化生长因子β mRNA表达均高于C组［（0.59+0.06）%比(0.38+0.03）%，（0.029 0±0.003 5）%比(0.018 0±0.002 2)%］，小鼠心肌细胞面积和β心肌肌球蛋白重链7阳性表达大于/高于C组［（318±14）μm比(226±31)μm，（0.081±0.002）%比（0.052±0.004）%］，差异均有统计学意义（均P＜0.05）。实时荧光定量聚合酶链反应检测结果显示，D组小鼠心脏组织中白细胞介素6、白细胞介素1β、肿瘤坏死因子α的mRNA表达均显著高于C组［（2.80±0.33）比(1.01±0.05),(2.10±0.41)比(1.03±0.06),(3.70±0.51)比(1.00±0.07）］；免疫组织化学和流式细胞检测显示，D组小鼠心脏组织中CD+45白细胞浸润显著高于C组［（6.30±0.46）比(3.80±0.17）］，差异均有统计学意义（均P＜0.05）。结论    单侧迷走神经切除促进AngⅡ介导的高血压心脏中胶原沉积、心肌肥厚和炎症因子的增加，CD+45白细胞浸润增加，迷走神经可抑制AngⅡ介导的高血压心脏纤维化进程。

• Objective    To observe the inhibitory effect of vagus nerve on cardiac fibrosis mediated by angiotensin Ⅱ(AngⅡ) in hypertensive mice. Methods    Thirty-six male, 12 weeks old C57BL/6 mice were randomly divided into 4 groups: sham operation＋0.9% sodium chloride solution infusion(group A), left vagotomy＋0.9% sodium chloride solution infusion(group B), sham operation＋AngⅡ infusion(group C), left vagotomy＋AngⅡ infusion(group D). Collagen deposition in cardiac mesenchyma was observed by Masson staining. Cardiomyocyte hypertrophy was observed by hematoxylin-eosin staining and wheat germ agglutinin staining. Expressions of tumor necrosis factor-α, interleukin-1β and interleukin-6 in heart tissue were tested by real-time fluorescence quantitative polymerase chain reaction（PCR）. Results    Systolic pressures of mice during 1-7 d after operation in group C and D were significantly higher than those in group A and B（P＜0.05）. Cardiac fibrosis area in group D was significantly larger than that in group C［（6.40±0.53）% vs （4.30±0.25）%］; expressions of α-smooth muscle actin mRNA and transforming growth factor-β mRNA in heart tissue of mice in group D were significantly higher than those in group C［（0.59+0.06）% vs (0.38+0.03）%， （0.029 0±0.003 5）% vs (0.018 0±0.002 2)%］; cardiomyocyte area and expression of β-cardiac myosin heavy chain-7 in group D were significantly larger/higher than those in group C［（318±14）μm vs (226±31)μm， （0.081±0.002）% vs （0.052±0.004）%］（all P＜0.05）. PCR showed that expressions of interleukin-6, interleukin-1β and tumor necrosis factor-α mRNA in heart tissue of mice in group D were significantly higher than those in group C［（2.80±0.33） vs (1.01±0.05), (2.10±0.41) vs (1.03±0.06), (3.70±0.51) vs (1.00±0.07）］（P＜0.05）. Immunohistochemistry and flow cytometry showed that CD+45 leukocyte infiltration in group D was significantly higher than that in group C［（6.30±0.46） vs (3.80±0.17）］（P＜0.05）. Conclusions    Unilateral vagotomy promotes AngⅡ-mediated cardiac collagen deposition, myocardial hypertrophy, inflammatory response and CD+45 leukocyte infiltration in hypertensive mice. Vagus nerve can inhibit the progress of angiotensin Ⅱ-mediated hypertensive cardiac fibrosis.